厦门大学学报（自然科学版）2026，Vol.65Issue(1)：68-80,13.DOI:10.6043/j.issn.0438-0479.202504016
机器学习在药物质量分析中的应用进展
Advances in machine learning applications for pharmaceutical quality analysis
摘要
Abstract
[Background]The rapid advancement of data science and artificial intelligence(AI)technologies has profoundly revolutionized pharmaceutical quality analysis,transforming traditional methodologies that predominantly relied on instrumental detection techniques such as chromatography and spectroscopy.These conventional approaches,while historically foundational,are often hampered by lengthy development cycles,subjective influences,labor-intensive procedures,limited real-time capabilities,and challenges in handling high-dimensional and complex sample matrices.Furthermore,the ever-tightening global regulatory standards mandate innovations that can meet higher demands for speed,accuracy,and comprehensive quality control.In this context,machine learning(ML),as a core subset of AI characterized by data-driven model construction capable of capturing nonlinear patterns and implicit relationships within large datasets,has emerged as a critical enabler for advancing pharmaceutical quality analysis.It offers powerful solutions for complex component identification,content quantification,process monitoring,and predictive modeling,thereby addressing key limitations of traditional analytical techniques and supporting the transition toward intelligent,automated,and continuous pharmaceutical manufacturing and regulation.[Progress]Over recent years,ML has demonstrated remarkable versatility and efficacy across various domains of pharmaceutical quality analysis,including small-molecule drugs,traditional Chinese medicine,and biopharmaceuticals.In the field of small-molecule drugs,ML techniques facilitate the optimization of chromatographic and mass spectrometric method development by establishing quantitative structure-activity relationships between molecular descriptors and instrumental responses.ML techniques also assist in in vitro-in vivo correlation modeling,as their robust data processing capabilities and nonlinear modeling advantages enable effective decoding of the complex interrelationships among various parameters influencing the in vivo behavior of certain drugs.ML-enabled approaches have also been successfully applied to the online monitoring of critical quality attributes,such as dissolution rates and particle morphology,through process analytical technology(PAT),providing real-time predictive feedback that facilitates adaptive process control and ensures batch-to-batch consistency.In traditional Chinese medicine,where the complexity and variability of multi-component systems pose significant analytical challenges,ML methods combined with imaging and spectral technologies are transforming quality assessment.Multimodal data fusion strategies,such as integrating hyperspectral imaging(HSI),enable rapid,nondestructive discrimination of herbal sources,identification of adulterants,and content determination of active and toxic constituents.These advances have substantially improved the accuracy and efficiency of authenticating herbal origins,detecting substandard or adulterated products,and predicting bioactive compound contents.For biopharmaceuticals,particularly monoclonal antibodies and recombinant proteins,ML techniques underpin the elucidation of complex post-translational modifications,notably glycosylation patterns,which critically influence efficacy and immunogenicity.Additionally,ML models assist in the prediction of biological activity based on structural features,enabling rational design and process optimization.Online monitoring of critical parameters such as aggregate levels and particle size distributions via image-based ML algorithms has also become feasible,fostering real-time quality assurance during manufacturing of biopharmaceuticals.[Perspective]The integration of ML into pharmaceutical quality analysis is poised to drive transformative change in the industry.Future research trajectories should focus on overcoming the current limitations by enhancing model transparency and interpretability to meet stringent regulatory standards.This includes developing explainable AI frameworks that elucidate the decision-making processes of complex models,thereby ensuring traceability and risk assessment in regulatory submissions.Concurrently,efforts should target constructing multi-modal,multi-scale datasets and process information,forming comprehensive digital twins of drug products throughout their lifecycle.Such systems will enable robust,real-time,end-to-end quality assurance and process optimization.Advances in sensor technology,miniaturization,and rapid detection methods will synergize with ML algorithms to realize real-time,in situ quality monitoring and predictive analytics at unprecedented scales and speeds.These developments will facilitate truly continuous manufacturing paradigms,where process deviations are detected and corrected instantaneously,thereby reducing waste,increasing efficiency,and ensuring consistent product quality.Moreover,the convergence of ML with blockchain and other traceability technologies will bolster data integrity and supply chain transparency,fostering greater regulatory confidence.Fostering interdisciplinary collaborations among data scientists,chemists,engineers,and regulators will accelerate the translation of innovative ML models from laboratory research into industrial applications.Ultimately,the integration of ML into pharmaceutical quality analysis will not merely optimize existing workflows but will unlock new paradigms of predictive,adaptive,and fully intelligent drug development and manufacturing systems,charting a new frontier toward personalized medicine and precision pharmacology.关键词
机器学习/药物质量分析/小分子药物/中药/生物药物Key words
machine learning/pharmaceutical quality analysis/small molecule medicine/traditional Chinese medicine/biopharmaceutical分类
医药卫生引用本文复制引用
冯嘉楠,商周怡,李萌,李嫣..机器学习在药物质量分析中的应用进展[J].厦门大学学报（自然科学版）,2026,65(1):68-80,13.基金项目
国家自然科学基金(82504740,22274025) （82504740,22274025）
上海市2024年度"科技创新行动计划"启明星培育项目(24YF2721000) （24YF2721000）
上海健康医学院教师教学研究项目(CFDY20250010) （CFDY20250010）
